With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality r...Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.展开更多
Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-c...Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.展开更多
Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases rangin...Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.展开更多
BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopatho...BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.展开更多
AIM:To review all of epidemiological aspects of nonalcoholic fatty liver disease(NAFLD) and also prevent this disease is examined.METHODS:We conducted a systematic review according to the PRISMA guidelines.All searche...AIM:To review all of epidemiological aspects of nonalcoholic fatty liver disease(NAFLD) and also prevent this disease is examined.METHODS:We conducted a systematic review according to the PRISMA guidelines.All searches for writing this review is based on the papers was found in Pub Med(MEDLINE),Cochrane database and Scopus in August and September 2014 for topic of NAFLD in Asia and the way of prevention of this disease,with no language limitations.All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed.RESULTS:NAFLD is the most common liver disorder in worldwide,with an estimated with 20%-30% prevalence in Western countries and 2%-4% worldwide.The prevalence of NAFLD in Asia,depending on location(urban vs rural),gender,ethnicity,and age is variable between 15%-20%.According to the many studies in the world,the relationship between NAFLD,obesity,diabetes mellitus,and metabolic syndrome(MS) is quiet obvious.Prevalence of NAFLD in Asian countries seems to be lower than the Western countries but,it has increased recently due to the rise of obesity,type 2 diabetes and MS in this region.One of the main reasons for the increase in obesity,diabetes and MS in Asia is a lifestyle change and industrialization.Today,NAFLD is recognized as a major chronic liver disease in Asia.Therefore,prevention of this disease in Asian countries is very important and the best strategy for prevention and control of NAFLD is lifestyle modifications.Lifestyle modification programs are typically designed to change bad eating habits and increase physical activity that is associated with clinically significant improvements in obesity,type 2 diabetes and MS.CONCLUSION:Prevention of NAFLD is very importantin Asian countries particularly in Arab countries because of high prevalence of obesity,diabetes and MS.展开更多
Autophagy is a lysosome-associated,degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.Hepatitis C virus(HCV)is a major cause of chronic hepatit...Autophagy is a lysosome-associated,degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.Hepatitis C virus(HCV)is a major cause of chronic hepatitis,which often leads to end-stage liverassociated diseases and is a significant burden on worldwide public health.Emerging lines of evidence indicate that autophagy plays an important role in promoting the HCV life cycle in host cells.Moreover,the diverse impacts of autophagy on a variety of signaling pathways in HCV-infected cells suggest that the autophagic process is required for balancing HCVhost cell interactions and involved in the pathogenesis of HCV-related liver diseases.However,the detailed molecular mechanism underlying how HCV activates autophagy to benefit viral growth is still enigmatic.Additionally,how the autophagic response contributes to disease progression in HCV-infected cells remains largely unknown.Hence,in this review,we overview the interplay between autophagy and the HCV life cycle and propose possible mechanisms by which autophagy may promote the pathogenesis of HCVassociated chronic liver diseases.Moreover,we outline the related studies on how autophagy interplays with HCV replication and discuss the possible implications of autophagy and viral replication in the progression of HCV-induced liver diseases,e.g.,steatosis and hepatocellular carcinoma.Finally,we explore the potential therapeutics that target autophagy to cure HCV infection and its related liver diseases.展开更多
Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortal...Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.展开更多
AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection.
We provide a concise review of the main epidemiological literature on fatty liver(FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already availa...We provide a concise review of the main epidemiological literature on fatty liver(FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.展开更多
We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT sh...We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus （HCV）. With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.展开更多
AIM: To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent feature associated with more severe liver damage, despite at...AIM: To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent feature associated with more severe liver damage, despite at least 6 mo of lifestyle changes.展开更多
AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with be...AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients’ ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload.展开更多
Nuclear erythroid 2-related factor 2(Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with th...Nuclear erythroid 2-related factor 2(Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with the antioxidant response element, which induces the expression of a variety of downstream targets aimed at cytoprotection. Previous studies suggested oxidative stress and associated damage could represent a common link between different forms of diseases. Oxidative stress has been implicated in various liver diseases, including viral hepatitis, nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease and drug-induced liver injury. Nrf2 activation is initiated by oxidative or electrophilic stress, and aids in the detoxification and elimination of potentially harmful exogenous chemicals and their metabolites. The expression of Nrf2 has been observed throughout human tissue, with high expression in detoxification organs, especially the liver. Thus, Nrf2 may serve as a major regulator of several cellular defense associated pathways by which hepatic cells combat oxidative stress. We review the relevant literature concerning the crucial role of Nrf2 and its signaling pathways against oxidative stress to protect hepatic cell from oxidative damage during development of common chronic liver diseases. We also review the use of Nrf2 as a therapeutic target to prevent and treat liver diseases.展开更多
AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from bo...AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden’s index.RESULTS: The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden’s index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden’s index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.展开更多
BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of h...BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.展开更多
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
基金supported by grants from the Research Foundation–Flanders(11A6420N,1268823N to WC and LVH)a FWO Junior Research Project Grant(G055121N to REV)VIB.AG is a senior clinical researcher of the Research Foundation–Flanders(1805718N)。
文摘Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.
基金supported by grants from the Natural Science Research Project of Shanxi Basic Research Program [20210302123246]the Scientific Research Project of Shanxi Provincial Health Commission [2020079]+1 种基金the Natural Science Foundation Youth Fund of Hebei Province[C2022402032]the Shanxi Province Higher Education “Billion Project” Science and Technology Guidance Project [BYJL036]。
文摘Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
文摘Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.
基金Supported by Chinese National 13th Five-Year Plan's Science and Technology Projects,No.2017ZX10202201.
文摘BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.
基金Gastroenterology and Liver Disease Research Center,Research Institute for Gastroenterology and Liver Diseases,Shahid Beheshti University of Medical Science
文摘AIM:To review all of epidemiological aspects of nonalcoholic fatty liver disease(NAFLD) and also prevent this disease is examined.METHODS:We conducted a systematic review according to the PRISMA guidelines.All searches for writing this review is based on the papers was found in Pub Med(MEDLINE),Cochrane database and Scopus in August and September 2014 for topic of NAFLD in Asia and the way of prevention of this disease,with no language limitations.All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed.RESULTS:NAFLD is the most common liver disorder in worldwide,with an estimated with 20%-30% prevalence in Western countries and 2%-4% worldwide.The prevalence of NAFLD in Asia,depending on location(urban vs rural),gender,ethnicity,and age is variable between 15%-20%.According to the many studies in the world,the relationship between NAFLD,obesity,diabetes mellitus,and metabolic syndrome(MS) is quiet obvious.Prevalence of NAFLD in Asian countries seems to be lower than the Western countries but,it has increased recently due to the rise of obesity,type 2 diabetes and MS in this region.One of the main reasons for the increase in obesity,diabetes and MS in Asia is a lifestyle change and industrialization.Today,NAFLD is recognized as a major chronic liver disease in Asia.Therefore,prevention of this disease in Asian countries is very important and the best strategy for prevention and control of NAFLD is lifestyle modifications.Lifestyle modification programs are typically designed to change bad eating habits and increase physical activity that is associated with clinically significant improvements in obesity,type 2 diabetes and MS.CONCLUSION:Prevention of NAFLD is very importantin Asian countries particularly in Arab countries because of high prevalence of obesity,diabetes and MS.
文摘Autophagy is a lysosome-associated,degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.Hepatitis C virus(HCV)is a major cause of chronic hepatitis,which often leads to end-stage liverassociated diseases and is a significant burden on worldwide public health.Emerging lines of evidence indicate that autophagy plays an important role in promoting the HCV life cycle in host cells.Moreover,the diverse impacts of autophagy on a variety of signaling pathways in HCV-infected cells suggest that the autophagic process is required for balancing HCVhost cell interactions and involved in the pathogenesis of HCV-related liver diseases.However,the detailed molecular mechanism underlying how HCV activates autophagy to benefit viral growth is still enigmatic.Additionally,how the autophagic response contributes to disease progression in HCV-infected cells remains largely unknown.Hence,in this review,we overview the interplay between autophagy and the HCV life cycle and propose possible mechanisms by which autophagy may promote the pathogenesis of HCVassociated chronic liver diseases.Moreover,we outline the related studies on how autophagy interplays with HCV replication and discuss the possible implications of autophagy and viral replication in the progression of HCV-induced liver diseases,e.g.,steatosis and hepatocellular carcinoma.Finally,we explore the potential therapeutics that target autophagy to cure HCV infection and its related liver diseases.
文摘Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
基金Supported by National High Technology Research and Development Program(863 Program)of China,No.2012AA021001
文摘AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection.
文摘We provide a concise review of the main epidemiological literature on fatty liver(FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.
文摘We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus （HCV）. With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.
基金Supported by Associazione Malattie Metaboliche del Fegato ONLUS(Non-profit organization for the Study and Care of Metabolic Liver Diseases),Centro Studi Malattie Metaboliche del Fegato,Universitàdegli Studi di Milano
文摘AIM: To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent feature associated with more severe liver damage, despite at least 6 mo of lifestyle changes.
基金Supported by The Gastrointestinal and Liver Disease Research Center of Tehran University of Medical Sciences
文摘AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients’ ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload.
基金Supported by The Scientific Research Projects from the Development and Reform Commission of Hunan Province,China,No.2011(1318),No.2012(1493)and No.2013(1132)
文摘Nuclear erythroid 2-related factor 2(Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with the antioxidant response element, which induces the expression of a variety of downstream targets aimed at cytoprotection. Previous studies suggested oxidative stress and associated damage could represent a common link between different forms of diseases. Oxidative stress has been implicated in various liver diseases, including viral hepatitis, nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease and drug-induced liver injury. Nrf2 activation is initiated by oxidative or electrophilic stress, and aids in the detoxification and elimination of potentially harmful exogenous chemicals and their metabolites. The expression of Nrf2 has been observed throughout human tissue, with high expression in detoxification organs, especially the liver. Thus, Nrf2 may serve as a major regulator of several cellular defense associated pathways by which hepatic cells combat oxidative stress. We review the relevant literature concerning the crucial role of Nrf2 and its signaling pathways against oxidative stress to protect hepatic cell from oxidative damage during development of common chronic liver diseases. We also review the use of Nrf2 as a therapeutic target to prevent and treat liver diseases.
基金Supported by GILDRCIran University of Medical Sciences
文摘AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden’s index.RESULTS: The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden’s index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden’s index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.
基金Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme,No.2013ZX10005002Beijing the Special Clinical Application Research and Translational Grants,No.Z151100004015221
文摘BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.
